This document summarizes various neurological effects of alcoholism. It discusses acute alcoholic intoxication, alcohol withdrawal including seizures, hallucinations, and delirium tremens. It also covers nutritional deficiencies that can occur like Wernicke-Korsakoff syndrome and neurological complications of uncertain etiology. Specific conditions related to alcoholism are explained such as encephalopathy, trauma, strokes and others. The effects of alcohol on neurotransmitter systems are outlined. Features of alcohol withdrawal syndrome and delirium tremens are defined. Management of withdrawal and complications are addressed.

1. ALCOHOLISM
IN
NEUROLOGY
-Dr. Sachin Adukia

2.  Acute alcoholic intoxication
 Alcohol withdrawal
 Withdrawal seizures
 Alcohol hallucinosis
 Delirium tremens
 Nutritional deficiencies:
 Wernicke-Korsakoff syndrome.
 Alcoholic polyneuropathy.
 Pellagra.
 Neurological complication of uncertain etiology:
 Alcoholic cerebellar degeneration
 Central pontine myelinolysis
 Marchiafava-Bignami disease
 Alcoholic amblyopia

3.  Encephalopathy:
 Hepatic encephalopathy
 Trauma:
 SDH
 Post stroke epilepsy
 Others:
 Stroke
 brain tumors
 Headache
 Hypoglycemia

4.  Alcohol
 facilitates inhibitory neurotransmitter GABA
 and inhibits excitation induced by NMDA
 It has effects on opioid, dopamine, and serotonin systems
 Sustained heavy consumption casues dependency and increased tolerance with
 reduced sensitivity to GABA
 increased sensitivity to NMDA

7.  Blood alcohol concentrations reflect rate of intake, degree of tolerance.
 Extreme intoxication (>300 mg/100 ml)
 increasing drowsiness and then coma
 depressed tendon reflexes
 hypotension, hypothermia, and slowed respiration
 Alcohol concentrations >400 mg/100 ml.
 Death may occur
 At < 400 mg/100 ml, look for alternative cause for coma
 head injury, other drug usage
 hypoglycemia, meningitis

8.  At a cellular level daily alcohol intake induces
 functional increase in NMDA receptor levels- excitatory
 When alcohol is stopped
 these excess receptors cause large calcium flux into cells,
hyperexcitability, and cell death.
 alcohol mediated inhibitory action of GABA reduces
 Increase in excitatory glutamate and drop inhibitory GABA give
noradrenergic ‘‘overdrive’’- sympathetic overactivity.

11. Alcohol-withdrawal syndrome
 with a long history of sustained alcohol use
 Symptoms after 4 -12 hrs after last consumption, may start upto 48 to 72 hrs esp.
delirium
 Initial symptoms –
 insomnia, anxiety, tremulousness, palpitations, diaphoresis
 Can appear even when significant alcohol level in blood is present.
 Minor symptoms - self-limited, symptoms peaking and resolving within 72 hours.
 Moderate to severe - urgent medical attention as they are complicated by
 withdrawal seizures
 alcoholic hallucinosis,
 delirium tremens- DT

12. Alcohol-withdrawal seizures
 Usually GTCS, occuring between 12 -48 hours from the last drink
 either a single seizure or brief flurry, usually self limiting
 Age group- Chronic alcoholics, 4th or 5th decade
 Status epilepticus –rare, but rates upto 9 - 25% observed
 Outcome more favourable, but recovery may be compounded by prolonged
post-ictal state.
 Investigation for structural, metabolic, infectious causes if:
 status epilepticus
 focal seizures
 or focal deficits in the postictal state
 recurrent or prolonged seizures require Rx.

13. Withdrawal seizures
 Diagnosis
 presence of other symptoms of alcohol withdrawal
 h/o recent alcohol misuse.
 ?? genetic susceptibility +
 Other factors presenting as seizure in alcoholics
 occult traumatic brain injuries
 parenchymal contusions
 subdural haematoma
 Subarachnoid haemorrhages
 Hypoglycemia
 Other substance abuse

14. Alcoholic hallucinosis- Distinct from DT
 hallucinations that develop within 12 to 24 hrs of abstinence
 resolve within 24 - 48 hrs (earliest point at which delirium
tremens develops)
 usually visual, my be auditory and tactile
 not a/w global clouding of sensorium, only specific
hallucinations
 Vital signs are usually normal

15. Alcohol withdrawal seizures left untreated progress to
delirium tremens in nearly one-third of patients

16. Delirium Tremens
 Defined by hallucinations, disorientation, tachycardia, HTN,
hyperthermia, agitation, and diaphoresis after acute reduction or
abstinence from alcohol.
 Begins between 48 -96 hrs after last drink,
 Lasts 1-5 days
 Mortality from DT < 5%, may be due to
 arrhythmia,
 complicating illnesses- pneumonia,
 or failure to identify problem that led to alcohol cessation:
 pancreatitis, hepatitis, or CNS injury or infection.

17. Risk factors for development of DT
 sustained drinking
 h/o previous DT
 Age > 30
 concurrent illness
 significant alcohol withdrawal in the presence of an elevated alcohol level
 A longer period since the last drink
 patients presenting with alcohol withdrawal >2 days after last drink
have DT more likely than those who present within 2 days)

18. Management
 Quiet room
 Mechanical restraints
 IVF
 Thiamine, multivitamins
 deficiencies of glucose, potassium, magnesium, phosphate corrected as
needed
 Caloric support
 Benzodiazepines- IV preferred, IM avoided d/t variable absorption
 Diazepam , lorazepam, chlordiazepoxide - most frequently used
 Longacting BZD with active metabolites (eg, diazepam or
chlordiazepoxide) preferred
 As they result in a smoother course with less chance of recurrent
withdrawal or seizures.

19. Use of sedatives
 Benzodiazepines
 First line therapy for ALL alcohol withdrawal syndrome
 Diazepam, 5-10 mg IV, repeat every 5 -10 min, Max 160/d OR
 Lorazepam, 2 to 4 mg IV, repeat every 15 to 20 minutes esp. in cirrhosis or acute
alcoholic hepatitis - due to short action and absence of active metaboite, no oversedation
 Barbiturates
 Synergistic with benzodiazepines; if refractory to high-dose BZD
 130 to 260 mg IV, repeat every 15 to 20 minutes
 Intubation frequently required with concurrent benzodiazepine and barbiturate use
 ALL patients requiring barbiturates – monitor in ICU
 Propofol
 Excellent agent if refractory to BZD and barbiturates
 Intubation almost always
 1 mg/kg IV push as induction agent for intubation and titrate

20. Refractory DT
 Is not clearly defined.
 May be present if > 50 mg diazepam or 10 mg lorazepam is
required to control withdrawal during 1st hour of treatment,
 or if > 200 mg of diazepam or 40 mg of lorazepam cant control
symptoms during initial 3 to 4 hrs of Rx
 Require
 Additional Phenobarbitone or propofol
 ICU admission

22. Not to be used in acute setting
 Such drugs include:
 Ethanol
 Antipsychotics (eg, haloperidol)
 Anticonvulsants (eg, carbamazepine)
 Centrally acting alpha2 agonists (eg, clonidine, dexmedetomidine)
 Beta blockers (eg, propranolol)
 Baclofen
 They can reduce freq and intensity of minor withdrawal
symptoms, but more data supports BZD for Sz, DT

23. PROPHYLAXIS
 Patients with
 a history of seizures,
 delirium tremens,
 prolonged, heavy alcohol consumption,
 minimally symptomatic or asymptomatic but admitted for other
reasons
 Can be prophylactically treated with oral chlordiazepoxide.
If severe symptoms develop, manage in standard fashion.

24. Wernicke’s encephalopathy
 Thiamine deficiency
 In 1881, Carl Wernicke described an acute encephalopathy characterized by
mental confusion, ophthalmoplegia, gait ataxia
 associated it with autopsy findings - punctate hemorrhages around 3rd and 4th
ventricles and the aqueduct
 Prevalence at autopsy
 0.4 to 2.8 % - general population in the West
 majority are alcoholic
 Upto 12.5% of alcohol abusers have WE
 Susceptibilty- F>M

25. Conditions associated with WE
● Chronic alcoholism
● Anorexia nervosa or dieting
● Hyperemesis Gravida
 Prolonged intravenous feeding without proper supplementation
● Prolonged fasting or starvation, or unbalanced nutrition, esp.
with refeeding
● GI surgery (especially bariatric surgery)
● Systemic malignancy
● Transplantation
● Hemodialysis or peritoneal dialysis
● AIDS

26. PATHOPHYSIOLOGY
 Thiamine is a cofactor for many enzymes in energy metabolism,
 transketolase, alpha-ketoglutarate dehydrogenase, pyruvate dehydrogenase
 Thiamine requirements depend on metabolic rate, greatest during periods of
high metabolic demand and high glucose intake.
 Thus the precipitation of WE in susceptible pts by IV glucose before
thiamine supplementation
 Deficiency initiates neuronal injury by inhibiting metabolism in brain regions
with high metabolic requirements
 BBB breakdown, NMDA receptor mediated excitotoxicity and increased
reactive O2 species induce neurotoxicity
 Deficiency in alcoholics results from:
 inadequate dietary intake, reduced GI absorption, decreased hepatic storage
and impaired utilization

27. Pathology
 Acute WE lesions - vascular congestion, microglial proliferation, petechial
hemorrhages.
 Chronic cases- demyelination, gliosis, and loss of neuropil with relative
preservation of neurons.
 Neuronal loss most prominent in the relatively unmyelinated medial thalamus
 Atrophy of the mamillary bodies - highly specific in chronic WE and Korsakoff
syndrome :- up to 80 percent of cases
 Lesions occur symmetrically surrounding 3rd and 4th ventricle, aqueduct
 Virtually all cases - The mamillary bodies
 Commonly affected - Dorsomedial thalamus, locus ceruleus, periaqueductal
gray, ocular motor nuclei, vestibular nuclei
 Less frequently - colliculi, fornices, septal region, hippocampus, cerebral cortex,
which may show patchy, diffuse neuronal loss and astrocytic proliferation
 selective loss of Purkinje cells at anterior superior cerebellar vermis

29. Clinical features
 Classic triad: (< 33%)
 Encephalopathy
 Oculomotor dysfunction
 Gait ataxia

30. Encephalopathy
 Profound disorientation, indifference, inattentiveness
 If these are less severe, higher cognitive testing shows impaired memory
and learning
 Some exhibit agitated delirium d/t concomitant ethanol withdrawal.
 < 5 % present with depressed consciousness,
 Untreated - progress through stupor and coma to death

31. Oculomotor dysfunction
 Reflect lesions of oculomotor, abducens, and vestibular nuclei.
 Usually occur in combination
 Nystagmus - MC, horizontal gaze evoked to both sides
 Vertical nystagmus may occur- evoked by upward, rather than
downward gaze
 LR palsy is virtually always bilateral.
 Conjugate gaze palsies, isolated vertical gaze palsy, INO, complete
ophthalmoplegia are rare.
 Pupillary abnormalities- sluggish or unequal pupils
 Advanced cases- complete loss of eye movements with miotic,
nonreactive pupils.
 Ptosis is uncommon.

32. Gait ataxia
 Primarily involves stance and gait
 likely d/t combination of
 Polyneuropathy
 Cerebellar involvement
 and vestibular dysfunction
 When severe, walking is impossible.
 Less affected patients walk with
 widebased gait and
 slow, short spaced steps.
 appreciated only on tandem gait in some
 Cerebellar pathology - restricted to the anterior and superior vermis;
 thus, ataxia of the legs or arms and dysarthria or scanning speech are uncommon
 Vestibular dysfunction - major cause of acute gait ataxia in WE
 also explains dissociation between gait and limb abnormalities

33. Other signs
 Evidence of protein calorie malnutrition
 Vestibular dysfunction without hearing loss is a common finding
 Peripheral neuropathy is common and typically involves just the lower
extremities
 gradual onset of weakness, paresthesias, and pain affecting the distal lower
extremities
 examination reveals diminished or absent ankle jerks and patchy distal sensory
loss.
 Hypothermia may cause unreactive pupils, rarely encountered in normothermic
patients with WE
 Lesions in the posterior and posterolateral hypothalamus - consistent with
thermoregulatory functions of the hypothalamus.
 While overt beriberi heart disease is rare in WE, other cardiovascular signs and
symptoms are common
 tachycardia, exertional dyspnea, elevated cardiac output, and EKG abnormalities

34. Diagnosis
 WE is diagnosed in patients with two of the following four Caine criteria
 Dietary deficiency
 Oculomotor abnormalities
 Cerebellar dysfunction
 Either altered mental status or mild memory impairment
 Caine criteria increased the diagnostic sensitivity for WE from 22% using the
classic triad, to 85%
 There are no laboratory studies that are diagnostic of WE.
 Thiamine deficiency - reliably detected by
 erythrocyte thiamine transketolase (ETKA) before and after thiamine
pyrophosphate (TPP).
 A low ETKA, along with a more than 25 percent stimulation, establishes the
diagnosis of thiamine deficiency
 Not necessary for diagnosis and management

35. Others
 CSF - normal or may show a mild protein elevation
 Pleocytosis or protein >100 mg/dL - alternative diagnoses
 EEG if NCSE suspected.
 In WE, only ½ pts demonstrate EEG abnormalities,
 usually diffuse mild to moderate slow wave activity

36. Imaging
 Not essential to diagnosis, shoud not delay Rx
 MRI is more sensitive than CT
 Typical findings include
 areas of increased T2 and FLAIR signals
 decreased T1 signal
 diffusion abnormality
surrounding the aqueduct and third ventricle
within medial thalamus, dorsal medulla, tectal plate, and
mamillary bodies
 Atypical areas - cerebellum, CN nuclei, dentate nuclei, caudate, red
nuclei, splenium and cerebral cortex

41. Treatment
 Immediate IV thiamine 500 mg over 30 minutes, TID for 2 days
 Then 250 mg IV or IM OD for an additional five days
 other B vitamins and magnsium
 Glucose without thiamine precipitates or worsen WE;. thus, thiamine
administered before glucose.
 GI absorption of thiamine is erratic in alcoholic and malnourished
patients, thus oral administration - unreliable initially
 Daily oral Thiamine 100 mg be continued

42. Treatment Outcomes
 Prompt thiamine - improvement in ocular signs within hours to days
 If ocular palsies fail to respond, other diagnoses should be considered.
 recovery of vestibular function may begin during 2nd week after thiamine
 gait ataxia coincides with recovery of vestibular function
 Confusion subsides over days and weeks.
 MRI abnormality resolves with clinical improvement
 This early therapeutic response likely represents the recovery from a
biochemical rather than a structural lesion.

43. Korsakoff syndrome
 Due to Thiamine deficiency in alcoholics, pts as a rule unaware of their illness
 Epidemiology- not well known
 undiagnosed Wernicke syndrome can progress to Korsakoff syndrome.
 Is distinguished from acute WE by
 prominent anterograde and retrograde amnesia
 without substantially impaired alertness and attention
 Without extraocular movement disturbance.
 Manifestations include
 anterograde amnesia, impaired ability to acquire or retain new information;
 prominent confabulation is due to inability to recall even a brief, simple story or recent
information.
 Retrograde amnesia is identified by the inability to recall elements of both recent and
remote memory

44.  significant degree of vacuous spontaneous speech and abulia - mistaken for
depressive symptoms
 Attention and social behavior are relatively preserved
May result when both the thalamus (particularly the anterior thalamic nucleus)
and hypothalamus (medial mammillary nucleus) are injured
 Patients with KS rarely recover.
 With thiamine, confabulation nmay resolv, amnesia persists
 Many patients require at least some form of supervision and social support,

45. Alcoholic polyneuropathy:
Nutritional , direct toxic effect of alcohol
 Peripheral distal sensorimotor neuropathy
 Chronic, well-fed alcoholics without vitamin deficiency
 develop slowly progressive sensory loss affecting small fiber- mediated
functions, especially nociception
 pain and burning paresthesia are common
 no ataxia or weakness from neuropathy
 Non-alcoholic thiamine deficiency produces prominent subacute weakness
and sensory ataxia from large-diameter > small-diameter fiber sensory
neuropathy
 Malnourished chronic alcoholics have features of both
 Patients may disregard minor paresthesia or anesthetic areas until significant
pain or gait difficulties evolve
 Ataxia difficult to differentiate from Alcoholic Cerebellar degeneration

46.  Autonomic symptoms, including orthostatic hypotension, impotence,
incontinence, hyper- or hypohidrosis :- May be present
 difficult to demonstrate at the bedside unless frank orthostatic hypotension is
present
 Electrodiagnostic testing shows typical evidence of an axonal sensorimotor
neuropathy.
 Sensory distal amplitudes are reduced, or potentials are unrecordable.
 Motor evoked amplitude may be reduced, but to a lesser degree.
 Patients may have behaviors, such as prolonged immobility or adverse body
positions :- increased risk of compression neuropathy
 Biopsy (Sural nerve) shows typical changes, but not indicated
 Adequate nutrition, multivitamin supplements and thiamine
 Ususally good recovery but some residual deficits persist

47. ALCOHOLIC CEREBELLAR DEGENERATION
 Chronic cerebellar syndrome related to degeneration of Purkinje cells in
the cerebellar cortex : Midline cerebellar structures-
 anterior and superior vermis predominantly affected, identical to WE
 Develops only after 10 or more years of excessive ethanol
 may be d/t combination of nutritional deficiency and alcohol neurotoxicity
 Majority complain of gait impairment- weakness, unsteadiness, or
incoordination in the legs
 Later, a minority incoordination and tremor in the arms, dysarthria, and
intermittent diplopia or blurred vision.

48.  Examination demonstrates features of midline cerebellar lesion
 ataxia of stance and gait, resembling that of acute alcohol intoxication
 Tandem walking is typically impossible, even with mild disease.
 Heel-knee-shin is abnormal, but finger-nose may show mild
abnormalities,
 more severe impairment of handwriting
 Mild dysarthria- slow, slurred speech
 Some have a coarse, rhythmic, 3 to 5 Hz postural tremor affecting the
fingers, arms, or thighs.
 Cognitive function usually unimpaired, except if prior WE.

49.  Absence of CN abnormalities differentiates from vascular
disorders of posterior circulation, mass lesions, and demyelinative disease.
 age of onset and clinical course differentiates from some of the SCA;
 MSA, including olivopontocerebellar degeneration, may be difficult to distinguish on
clinical grounds alone
 Diagnosis - clinical history and neurologic examination
 CT or MRI scans may show cerebellar cortical atrophy,
 but one half of alcoholic patients with this finding are not ataxic on examination
 PET - shows reduction in cerebral metabolic rate for glucose and decrease in BZD
receptor binding in the superior cerebellar vermis :
 magnitude of hypometabolism correlates with the clinical severity
 Treatment: Cessation and supplementation, but ataxia persists in most

52. Ventricular Enlargement and Cognitive Dysfunction
 50 to 70 % alcohol abusers have cognitive deficits on neuropsychological
testing
 Ethanol neurotoxicity may contribute to this
 CT / MRI show enlargement of the cerebral ventricles and sulci in majority
of alcohol abusers.
 But do not correlate consistently with duration of drinking or severity of
cognitive impairment
 hypothesized that changes in brain parenchyma, but not brain water, accounts
for reversible radiographic and cognitive abnormalities of alcoholics
 Regional vulnerability:-
 Superior frontal cortex corrobrated by regional hypometabolism on PET
studies
 correlates with deficits in working memory in alcohol abusers
 White matter regional pathology is reveersible with abstinence

54.  Cetral pontine myelinolysis
 As they have poor energy reserves, Na-K-ATPase pump which
regulates osmolyte transport across neuronal membrane fails,
demyelination ensues
 Marchiafava Bignami disease
 rare disorder of demyelination or necrosis of corpus callosum and
adjacent subcortical white matter
 predominantly in malnourished alcoholics
 acute, subacute, or chronic
 marked by dementia, spasticity, dysarthria, inability to walk
 Patients may lapse into coma and die

57. Alcohol amblyopia
 far less common
 presents as a painless bilateral loss of vision in alcohol abusers
 Almost all c/o blurring or dimness of vision and of difficulty in reading small
prints.
 disease usually evolves over several weeks to months
 Fundus- may be normal or
 mild to moderate pallor of optic nerve heads; most apparent in temporal half
 stigmata of undernutrition is encountered
 Improvement almost always with adequate dietary and vitamin intake.

59. Acute and chronic alcoholic myopathy
 In two different studies, > 50 to 60 % alcoholi abuusrs had biopsy evidence of myopathy
 Skeletal muscle can be damaged by the administration of alcohol to wellnourished
volunteers ? Direct toxicity
 Electrolyte abnormalities - ?? hypokalemia, also impair skeletal muscle function

60. Acute myopathy
 develops over hours to days, often in relation to an alcoholic binge
 characterized by weakness, pain, tenderness, and swelling of affected muscles.
 ?? fasting during a binge may precipitate muscle injury
 majority are men
 Proximal most severely involved, but can be asymmetric or focal.
 Dysphagia and CCF may occur
 Laboratory findings- moderate to severe elevation of CK, myoglobinuria,
 EMG- fibrillations and myopathic changes
 Biopsy - muscle fiber necrosis on biopsy
 Treatment is directed at correcting cardiac arrhythmias, renal failure due to
rhabdomyolysis, and electrolyte distr.
 Abstinence - gradual, often partial, recovery

62. Chronic alcoholic myopathy
 evolves over weeks to months, is more common
 Pain < than in acute alcoholic myopathy, but muscle cramps may occur.
 Examination major findings are muscle weakness and atrophy, which affect
predominantly hip and shoulder girdles
 polyneuropathy coexists in many
 But clinical and laboratory features indicate a primary disturbance of muscle.
 Serum CK < in acute alcoholic myopathy, and myoglobinuria does not occur.
 Cessation improvement,
 continued alcohol abuse clinical deterioration

63. Hepatic encephalopathy
 Clinical triad
 West Haven stages of hepatic encephalopathy & Rx

65. Stroke
 Light to moderate use (up to two drinks a day for men and one for
women)
 elevates HDL concentration and reduced risk
 heavy alcohol consumption - increased risk for total stroke.
 cardiogenic brain embolism.
 Increased risk for hemorrhagic stroke
 alcohol-induced hypertension predisposes to spontaneous ICH
 active drinkers - higher freq. OSA with more severe hypoxemia.
 recommended to cease or reduce consumption for heavy drinkers.

66. Headache- Immediate or delayed
 May trigger cluster headache
 Immediate alcohol related headache:- Defined by HIS
 Occuring within 3 hrs of ingestion, resolving within 72 hrs of cessation of
alcohol
 Atleast one of the following:
 Bilateral
 Fronto-temporal
 Pulsatile
 Aggravtion by physical activity
 Amount independent of previous h/o migraine
 Delayed headache:
 Same character, but occurs when blood alcohol level drops or reduces to zero

67. Brain tumor
 Because beer and liquor contain nitrosamines,
 ?? Alcohol may increase the risk
 However, no consistent association between different types of alcohol and risk
of gliomas or meningiomas in
 childhood (maternal consumption)
 or adulthood.

68. References
 Daroff RB, Jankovic J, Mazziotta JC, Pomeroy SL. Bradley's neurology in
clinical practice. Elsevier Health Sciences; 2015 Oct 25.
 McIntosh C, Chick J. Alcohol and the nervous system. Journal of Neurology,
Neurosurgery & Psychiatry. 2004 Sep 1;75(suppl 3):iii16-21.
 Noble JM, Weimer LH. Neurologic complications of alcoholism.
CONTINUUM: Lifelong Learning in Neurology. 2014 Jun 1;20(3, Neurology of
Systemic Disease):624-41.
 Uptodate website 2017

69. Thank you